Risk factors predisposing to psychotic symptoms during levetiracetam therapy:A retrospective study

Purpose: While levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated.Methods: In our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepileptic drug use, and cognitive abilities. Univariate comparisons were performed, and variables with p &lt;0.1 were selected for binary logistic regression analysis.Results: The total incidence of psychosis during LEV therapy in our population was 3.7%. The timing of psychotic symptoms was classified as postictal in 20 (19.8%), interictal in 14 (15.4%), postepilepsy surgery in 1 (1.1%), and unknown in 18 cases (19.8%). In 31 cases (34.1%), psychotic symptoms were classified as an antiepileptic druginduced psychotic disorder (AIPD) as a result of LEV. In 7 cases (7.7%), AIPD occurred as a result of a different antiepileptic drug. A significant association was found between the experience of psychotic symptoms and status epilepticus (p = 0.002), a history of psychotic symptoms (p &lt;0.000), a history of psychiatric illness other than psychosis (p = 0.010), and concomitant phenytoin (PHT) usage (p = 0.044). Cotherapy with lamotrigine (LTG) was protective (p 0.042). A separate analysis of controls and exclusively the 31 cases with LEV-induced AIPD yielded comparable results; a significant association was confirmed with status epilepticus (p = 0.021) and history of psychotic symptoms (p 0.018), as well as with female gender (p 0.047) and intellectual disability (p = 0.043).Conclusion: Our retrospective study found that psychotic symptoms during LEV therapy were significantly associated with status epilepticus, a history of psychotic symptoms, a history of psychiatric illness other than psychosis, and concomitant PHT usage, whereas concomitant LTG usage was protective. Psychotic symptoms specifically as an adverse drug reaction to LEV were significantly associated with female gender, intellectual disability, status epilepticus, and a history of psychotic symptoms. (C) 2019 Elsevier Inc. All rights reserved.</p

Brivaracetam for the treatment of refractory epilepsy in patients with prior exposure to levetiracetam:A retrospective outcome analysis

PURPOSE: To determine whether brivaracetam (BRV) provides an evident improvement in treatment efficacy and a reduction in treatment-emergent adverse events (TEAEs) in patients with refractory epilepsy, who previously failed treatment with levetiracetam (LEV). DESIGN: Retrospective analysis of data extracted from electronic patient files at Epilepsy Centre Kempenhaeghe (Heeze, the Netherlands) from the year 2000 until October 2020. METHODS: The inclusion criteria were met by 407 patients >18 years of age. During data collection, 26 patients were excluded due to too little follow-up information on the use of either LEV or BRV, and two more due to poor medication compliance, leaving a total of 379 patients for further analyses. All had used LEV before they started treatment with BRV. For every patient, data were collected including demographic information, efficacy (positive responder or non-responder) of LEV and BRV, and TEAEs occurring during LEV and BRV treatment. RESULTS: A total of 121 (29.8%) patients had discontinued BRV treatment before the end of data collection. At time of data collection the mean time since first seizure was 25.4 years. Of the 379 patients, 82.8% were diagnosed with focal epilepsy and 9.8% with generalized epilepsy. The median duration of treatment was 39 months for LEV and 20 months for BRV, the mean maximum dose was 1749.9 mg/day for LEV and 144.2 mg/day for BRV, and the mean number of concomitant AEDs was 1.4 at the start of LEV treatment and 2.0 at the start of BRV treatment. LEV was switched directly to BRV in 208 (54.9%) patients; 171 (45.1%) patients had an interval between discontinuation of LEV and the start of BRV. The mean duration of interval was 77.7 months. Of the patients who discontinued BRV, 30 (24.8%) switched back to LEV. Discontinuation of initial LEV treatment was due to TEAEs in 63.6% of patients, including 55.1% because of behavioural TEAEs. Discontinuation of BRV was due to inadequate efficacy in 24.0% of patients, to TEAEs in 47.1% and to both inadequate efficacy and TEAEs in 22.3%. Concerning efficacy, the analysis showed no significant difference between the positive responder rate of LEV and BRV (72.0% vs 69.1%, p>0.05). Of the patients who were positive responders to LEV treatment, 78.0% also had a positive response to BRV treatment. Of the non-responders to LEV treatment, 46.2% did have a positive response to BRV treatment. In comparison to LEV, patients reported significantly fewer TEAEs during BRV treatment (86.5% vs 61.7%, p<0.05). The most substantial difference was seen in the category 'behaviour' (55.1% vs 22.4%, p<0.05). Newly found behavioural TEAEs after switching from LEV to BRV were found in 7.1% of patients. CONCLUSION: Overall BRV was better tolerated than LEV, especially regarding the behavioural TEAEs. Efficacy analyses showed that patients are likely to have a positive response to BRV when they had a positive response to LEV. However, this is not always guaranteed. Lack of response to LEV does not preclude a positive response to BRV. All in all, BRV seems to be an interesting treatment option in patients previously treated with LEV

A model of healthy aging based on smartphone interactions reveals advanced behavioral age in neurological disease

Action Contro

Economic evaluations of nonpharmacological treatments for drug-resistant epilepsy:A systematic review

This study was undertaken to systematically identify and critically appraise all published full economic evaluations assessing the cost-effectiveness of nonpharmacological interventions for patients with drug-resistant epilepsy. The Population, Intervention, Comparison, Outcome, Study criteria was used to design search strategies for the identification and selection of relevant studies. Literature search was performed using the MEDLINE (via PubMed), Embase, International Health Technology Assessment, National Institute for Health Research Economic Evaluation Database, and Cost-Effectiveness Analysis Registry databases to identify articles published between January 2000 and May 2023. Web of Science was additionally used to perform forward and backward referencing. Title, abstract, and full-text screening was performed by two independent researchers. The Consensus Health Economic Criteria (CHEC) checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 were applied for quality assessment. A total of 4470 studies were identified, of which 18 met our inclusion criteria. Twelve of the studies conducted model-based economic evaluation, and others were trial-based. Three studies showed that epilepsy surgery was cost-effective in adults, whereas this remained inconclusive for children (two positive, three negative). Three studies showed negative economic outcome for ketogenic diet in children. One of four studies showed positive results for self-management. For vagus nerve stimulation, one study showed positive results in adults and another one negative results in children. One recent study showed cost-effectiveness of responsive neurostimulation (RNS) in adults. Finally, one study showed promising but inconclusive results for deep brain stimulation (DBS). The mean scores for risk of bias assessment (based on CHEC) and for reporting quality (CHEERS 2022) were 95.8% and 80.5%, respectively. This review identified studies that assessed the cost-effectiveness of nonpharmacological treatments in both adults and children with drug-resistant epilepsy, suggesting that in adults, epilepsy surgery, vagus nerve stimulation, and RNS are cost-effective, and that DBS and self-management appear to be promising. In children, the cost-effectiveness of epilepsy surgery remains inconclusive. Finally, the use of ketogenic diet was shown not to be cost-effective. However, limited long-term data were available for newer interventions (i.e., ketogenic diet, DBS, and RNS)

Efficacy and tolerability of brivaracetam in patients with intellectual disability and epilepsy

Patients with intellectual disability (ID) are often excluded from clinical trials, and little is known about the best approach to treat their epilepsy. Brivaracetam (BRV) is a new antiepileptic drug (AED) for adjunctive treatment in patients with focal-onset seizures with or without secondary generalization. We analyzed the efficacy and tolerability of BRV in patients with ID and epilepsy who either had or had not previously received treatment with levetiracetam (LEV). Data on efficacy and tolerability were retrospectively collected. After the initial start of BRV in our tertiary epilepsy center, we analyzed medical records at 0, 3, 6 and 12 months of follow-up. 116 patients were included (mean age = 34.9 years, 44% female). All had complete data of 3-month follow-up, 76 of 6-month follow-up, and 39 patients of 1-year follow-up. Median starting dose of BRV was 50.0 mg/day and the mean number of concomitant AEDs was 2.6. Seizure reduction and no side effects were reported in more than half of all patients. The most reported side effects were somnolence, dizziness and aggression. Retention rates for BRV were 84.4%, 75.5% and 58.1% after 3, 6 and 12 months, respectively. Seizure reduction and side effects did not differ significantly between the groups with or without previous LEV treatment. We demonstrate that BRV is effective and well tolerated in patients with epilepsy and ID, even in those where previous LEV treatment failed

The ketogenic diet as a treatment option in adults with chronic refractory epilepsy: Efficacy and tolerability in clinical practice

The ketogenic diet (KD) is a high-fat, low-protein, low-carbohydrate diet that is used as a treatment for patients with difficult-to-control epilepsy. The present study assesses the efficacy and tolerability of the KD as an add-on therapy in adults with chronic refractory epilepsy. 15 adults were treated with the classical diet or MCT diet. During a follow-up period of 1 year we assessed seizure frequency, seizure severity, tolerability, cognitive performance, mood and quality of life (QOL). We found a significant reduction in seizures among the patients who followed the diet at least 1 year (n=5). Of these 5 patients, 2 had a reduction between 50 and 90%. Analyzing the study months separately, we found a seizure reduction of &gt;= 50% in 26.6% of the patients during at least 1 month of treatment. Common side-effects were gastrointestinal disorders, loss of weight and fatigue. There was a considerable, non-significant improvement found in mood and QOL scores. Improvements were independent of reduction in seizure frequency, indicating that the effects of the KD reach further than seizure control

The Cognitive Profile of Ethosuximide in Children

Introduction: Although ethosuximide is one of the oldest antiepileptic drugs (AEDs), little information is available about the cognitive side effects of ethosuximide. Objective: The aim of this study was to investigate the cognitive profile of ethosuximide. Methods: In this cross-sectional study, we used an extensive neuropsychological test battery in patients with epilepsy aged 6–16 years who were treated with monotherapy ethosuximide. We evaluated the efficacy of the drug by seizure frequency (seizure free or not). Results: We included 61 patients with a mean age of 9.4 years [standard deviation (SD) 2.7] who used on average 686 mg/day (SD 245) ESM as monotherapy. ESM was effective in the majority of the patients (70 % were seizure free for at least 6 months at moment of inclusion). The total study population showed impairments of intelligence, visuomotor, and attentional function including activation/alertness. Comparisons between the well-controlled patients and patients who were not in remission showed significantly lower intelligence values and lower performance on the visual-perceptual and attentional tasks for the group with ongoing seizures. Our results suggested that the higher order cognitive dysfunctions (such as intelligence and visual-perceptual functions) may be regarded as seizure or aetiology effects and that the impaired fluid cognitive functions, such as activation/alertness, sustained auditory attention and attentional control or switching, were due to ESM. Conclusion: This study suggests the attentional dysfunction resulting in psychomotor slowing and alertness deficits may be regarded as effects of ethosuximide. Although no untreated baseline assessment was available, these effects are comparable to those of other AEDs, and ethosuximide may therefore be considered an AED with only mild effects on cognition. As ethosuximide is a first-line therapy for absence seizures in childhood, and drug-induced cognitive impairment may interfere with development, learning, and academic achievement, these findings are of interest to clinicians who prescribe this drug, especially when informing parents